Gore A (Genetics) will perform the following services: Service 1: Manage clinical samples Core A will coordinate the retrieval of blood and cheek cell samples from the 3000 cases and controls stored in the Channing Laboratory biorepository and the preparation of DMA from these samples. Service 2: Perform mutational analysis of candidate genes. Core A will use direct DNA sequence analysis to identify DNA sequence variants in 34 candidate genes chosen on the basis of roles in calcium, oxalate, urate, and citrate homeostasis. SNP data from these genes will be used by Projects 1 and 2 for studies of the effect of genetic variants on protein function as well as the epidemiologic studies of Project 3. Service 3: Genotype variants (cSNPs defined as above and tagging SNPs) in 1500 stone formers and 1500 controls. Core A will manage the SNP genotyping efforts of this program. This will include cSNPs (identified as above) and a set of tagging SNPs. The genotyping of other polymorphisms of specific interest to individual projects will also be performed by the Core. Service 4: Maintain database and public website. Dissemination of the large volume of genetic data generated will be an important goal of this Program Project. The core will maintain a database of all genetic information obtained via Services 2 and 3. A publicly accessible website will make data quickly available to the outside community. Service 5: cDNA construct production. Design, construction, mutagenesis, and verification of cDNA clones for expression studies in Projects 1 and 2 will be performed in Core A. The Core will also develop additional expression constructs to facilitate outside collaborations. Service 6: Mouse genotyping. Projects 1 and 2 will require ongoing mouse DNA preparation and genotyping. This genotyping will be performed by Core A in order to increase quality control and efficiency of mouse analyses. In summary, the core will facilitate efforts of the Projects by coordination of genomic DNA preparation, sequencing, and genotyping (human and mouse studies), facilitation of the functional examination of gene variants via construct production, and management of data sharing with outside investigators.